Total Synthesis of Hinduchelins A-D, Stereochemical Revision of Hinduchelin A, and Biological Evaluation of Natural and Unnatural Analogues.

ABSTRACT

Here, we report the first total synthesis of hinduchelins A-D, a family of nontoxic catechol derivatives from Streptoalloteichus hindustanus, possessing a druglike chemotype and modest iron-chelating ability. A concise synthesis was developed employing methyl 5-methyloxazole-4-carboxylate as a single starting material to provide hinduchelins A-D (and unnatural analogues) in only four steps and 5-15% overall yields; moreover, the stereochemistry of hinduchelin A was reassigned from ( S) to ( R). Biological evaluation confirmed that natural and unnatural hinduchelins are weak iron chelators (siderophores).